In last few years, the understanding of the science of personal cleansing (skin and hair) has seen good advances. Skin, the largest organ in human body, is made up of two layers, dermis and epidermis. Epidermis is the outer layer and it is made up of several layers that have viable cells in different stages of differentiation. The viable keratinocytes of inner layers differentiate to non-nucleated, dead corneocytes to form the uppermost layer of epidermis called the stratum corneum (SC). The stratum corneum regulates the loss of water from human body and also protects the insides of human body from the external ravages. The stratum corneum is best described by the ‘brick and mortar’ model where the dead corneocytes are the bricks and the lipid bilayers are the mortar that forms the continuous domain. Both, human skin and hair gather dirt and microbes from the environment along with its own secretions of sebum. The centuries-old cleansers, like traditional soaps with very highly alkaline pH, not only swell the proteins of corneocytes but they do remove both proteins and lipids and disturb stratum corneum's function of controlling moisture leading to dryness, after-wash tightness, erythema and irritation. Cleansers are supposed to cleanse the skin of dirt, sebum and bacteria. Cleansing process also helps the natural exfoliation and rejuvenation of skin. However, when the cleansers start stripping the skin (SC of epidermis) of its lipids, proteins and natural moisturizing factor (NMF) then the skin's (stratum corneum's) function of balancing moisture is seriously compromised. This is what precisely happens with cleansers that contain very harsh and penetrating type of surfactants like soaps (sodium salt of fatty acids) and fatty alcohol sulphates (sodium dodecyl sulphate). (“The induction of skin tightness by surfactants”; M. Kawai and G. Imokawa; J. Soc. Cosmet. Chem. 147-156, 35(1984)). Needless to say that, cleansing with harsh surfactants is a bad choice for the sensitized and diseased skin. Better understanding of biology of skin in the last decade or so, helped formulators design cleanser systems that would be gentle on the skin. This understanding helped scientists in designing the surfactant structure that would do less damage to skin while cleansing. This deeper understanding of skin biology vis-à-vis skin cleansing resulted in emergence of “mild” surfactants and the exploitation of the synergy amongst surfactants to achieve the optimal cleansing without compromising skin's natural function. The science of skin cleansing is more or less true with hair's cleansing since structurally, hair are made up of again proteins and lipids, the percentage of protein, is obviously more as compared to skin's stratum corneum.
Mild cleansing for skin needs to be understood in the context of disrupting the normal biological structure of skin. Surfactants that are used for cleansing are classified in three main categories, e.g. anionic, amphoteric and nonionic. The cleansing and foaming properties of a surfactant depend on its nature (ionic or nonionic), the size of head group and subsequent aggregate (micelle) formation in solution.
The different types of surfactants have different interactions with skin's stratum corneum. Thus, three important constituents of stratum corneum that should not be disturbed during cleansing operations are a) proteins of corneocytes b) lipids of SC and c) NMF (natural moisturizing factor). For examples, ionic surfactants like anionic sodium dodecyl sulphate (SDS) or sodium lauryl ether sulphate (SLES) interact strongly with proteins of conmeocytes and cause irritation as a result of denaturation of proteins. In contrast to the above, electrically neutral zwitterionic surfactants, like cocoamidopropyl betaine (CAPB), interact far less with SC's proteins. Similarly, the non-ionic surfactants like alkyl polyglucosides have the least interaction with SC's proteins and hence they are almost non-irritants. The ionic surfactants (both anionics and cationics) are on the top of the list of substances with the irritation potential. For this reason, the anionic surfactant like SLES has been blended with zwitterionic CAPB for skin cleansing body washes. (“The inhibitory effect of some amphoteric surfactants on the irritation potential of alkyl sulphates”; Dominguez J. G., Balaguer F., Parra J. L., Palegero C. M., Int. J. Cosmet. Soc. 57-68, 3(2) (1981)). It is to be noted here that any surfactant, particularly soap type anionic sodium laurate with highly alkaline pH, is extremely harsh on skin since it is totally incompatible with the biological pH of stratum corneum which is acidic around 5 to 6. In addition, the high alkalinity of soap (pH of around 10 and above) swells the protein of corneocytes and often times intercalation of surfactant molecules in upper layers of SC causes further irritation (“Interaction of keratinous proteins with sodium lauryl sulphate”: I. Sorption; Faucher J. A., Goddad E. D., J. Soc. Cosmet. Chem. 323-338 29, (1978)). Another very important interaction that needs to be taken into consideration while evaluating mildness of a surfactant on skin is that the reaction between surfactants and lipid bilayers of SC that form the continuous domain in which the corneocytes are embedded. Lipids are of complex nature and the main constituents are ceramides, cholesterol and its derivatives and fatty acids. (“Surfactants-induced depletion of ceramides and other intercellular lipids: implication for the mechanism leading to dehydration of stratum corneum”; Imokawa G. Exogeneous Dermatology, 81-98 3, (2004)). Some lipid components get easily removed by micellar solubilization and causing serious damage to SC's barrier function and modulation of transepidermal loss of water (TEWL) to the environment. Serious consequences are seen as a result of stripping away of SC's lipids (increase in TEWL, after-wash skin tightness, dryness, erythema, xerosis, cracking of skin and loss of visco-elastic (flexibility and extensibility) properties of healthy skin. It should be noted that some of the surfactants have ‘mild interaction’ with proteins of corneocytes and are rated as ‘mild’ on the scale of irritancy, like zwitterionic cocoamidopropyl betaine (CAPB) or non-ionic alkyl polyglycosides (APG). However, these two classes of surfactants are very good lipid solubilizers and hence damage the lipid bilayers of SC through micellar solubilization. So a good personal cleanser should foam and lather well (consumer desired in-use attributes) and should remove soil, dirt and bacteria on skin without damaging or altering (least surfactant induced damage) the three constituents of SC e.g. proteins, lipids and NMF. (“Cleansing without compromise”: The impact of cleansers on the skin barrier and the technology of mild cleansing; Ananthapadmanabhan K. P., Moore D. J., Subramanyan K.; Dermatol. Ther. 16-26, 17 (2004)). So while selecting surfactants for skin cleansers formulators have to think about strategies to restore the hydration level as well the lipids lost during cleansing. The body wash formulation that meets the above criteria has been introduced to consumers in 2009. This formulated product was based on O-acyl isethionate (sodium cocoyl isethionate) as the mild surfactant. (“A novel technology in mild and moisturizing cleansing liquids”; K. P. Ananthapadmanabhan, L. Yang, C. Vincent, L. Tsaur et al.; Cosmet. Dermatol. 307-316, 22(6), (2009)). Subsequently, it has been shown that the combination of O-acyl isethionate and N-acyl amino acid surfactants is the most ideal for its mildness on the skin and good in-use attributes (A novel glycinate based body wash: clinical investigation into ultra-mildness, effective conditioning and improved consumer benefits. J. Regan, L-M Mollica, K. P. Ananthapadmanabhan, J. Clinical and Aesthetic Dermatology, 23-30, 6(6), (2013)).
This technology has been covered by U.S. Pat. No. 8,268,767 (2012) and U.S. Pat. No. 8,114,824 (2012) wherein the synergy of sodium cocoyl isethionate and sodium cocoyl glycinate has been exploited. The surfactant combinations comprising of O-acyl isethionates and N-acyl glycinates or N-acyl sarcosinates as main ingredients have been reported to be very good cleansing systems that are ‘super mild/gentle’ on skin and excellent delivery vehicles of actives (benefit agents like emollients, silicones, triglycerides and petrolatum).
K. P. Ananthapadmanabhan et al. have shown the synergy of sodium cocoyl isethionate and sodium cocoyl glycinate in getting the best of mildness and in-use performance for skin cleansers (J. Clinical and Aesthetic Dermatology, 23-30, 6(6), (2013)). Koshti et al. (PCT/IN2013/000494) demonstrated a novel way of getting the two classes (O-acyl isethionates and N-acyl amino acid surfactants) of mild surfactants manufactured as aqueous solutions in a pseudo one-pot process. In view of the synergy between sodium cocoyl isethionate and sodium cocoyl glycinate as demonstrated by K. P. Ananthapadmanabhan et al., this combination has been further studied by Kshirsagar et al. (Isotropic, flowable, skin-pH aqueous compositions comprising N-acyl glycinates as primary surfactants, Indian Patent application no. 2715/MUM/2014) wherein it has been demonstrated that using third surfactant it is possible to create clear, transparent formulations with pH similar to skin (pH of 5.0 to 6.0).
However, the major limitation for the formulations based on N-acyl glycinate as the primary surfactant as proposed by Kshirsagar et al. is that at skin pH which is on the acidic side, N-acyl glycinate gets converted in to N-acyl glycine which is insoluble in water. Thus, acyl glycinate's going to acyl glycine form significantly reduces its surfactant properties. The formulations where acyl glycinate is used as primary surfactant tend to become hazy since acyl glycine acts like a typical hydrophobe and achieving absolute transparency at skin-pH is not possible. In addition, when acyl glycinate goes to acyl glycine (equation 1 below), it adversely affects the foaming property. This foam depression and very quick lather drainage is observed in the presence of other surfactants, particularly, the mild acyl isethionates as well. Thus, combination of two mild surfactants, N-acyl glycinate (primary surfactant, Kshirsagar et al.) and O-acyl isethionate at acidic skin pH does not give consumer desired in-use attributes of good foam and lather. Thus, achieving transparency at skin pH and the consumer desired in-use attributes are not possible with combination of only glycinate-Isethionate wherein acyl glycinate is used as primary surfactant.

The inventors of the present invention surprisingly found that mild surfactant composition produced by the pseudo one pot synthesis wherein two classes of mild surfactants are produced in one pot from a single fatty raw material by reacting other reactants in sequential manner and adding lipidated glycines (Example 1) solved the problems of designing the cleansing end-formulations which have pH similar to skin's pH, mild to skin, preservative free and yet transparent.
Also due to the synergistic amplification of surfactants properties, namely foam volume and lather potential, even less amount of surfactants provides the desired performance in end formulations.